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Long-acting injectable (LAI) formulations of second-generation antipsychotics (SGA) are a mainstay in the treatment of schizophrenia-spectrum patients, and their use improves adherence and reduces relapse risk. Personalizing LAI-based therapy involves tailoring the transition from oral to LAIs based on individual and drug-related pharmacokinetic peculiarities. We discuss pharmacokinetic considerations as a cornerstone of a smooth transition from oral to LAI SGAs based on works identified using an updated search in PubMed and Embase in February 2023. Establishing the extent of antipsychotic exposure during oral SGA-treatment from the patient’s SGA levels is often a more appropriate orientation method to choose the equivalent LAI dose than population-based data. Oral dose adjustment during LAI transition can also be guided by checking SGA levels before the LAI injection. LAI SGAs may dominate the maintenance treatment of schizophrenia-spectrum disorders with increased use for other severe mental illnesses such as bipolar disorder. Spurring this trend is the development of newer formulations with longer injection intervals and increased administration ease, but transitioning from oral SGA remains a challenge. By understanding the pharmacokinetics of LAI formulations and measuring SGA levels during oral therapy, one can personalize/optimize the switch from oral SGAs to LAI counterparts.

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